Abstract
To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18-65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092 ) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.
Keywords: AKS-452; COVID-19; Coronavirus; Fc-fusion; Infectious disease; Pandemic; Prophylaxis; SARS-CoV-2; Vaccine.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, pandemic, Infectious disease, Prophylaxis, vaccine., AKS-452, Fc-fusion, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, Vaccine, coronavirus, vaccination, reactogenicity, Open-label, Phase I, SARS-CoV-2 variant, Infection, Infectious disease, severe acute respiratory syndrome Coronavirus, anti-SARS-CoV-2, viral infections, Spike protein, Receptor binding domain, Antigen, Prophylaxis, Cohort, Viral, Alpha, Subunit vaccine, mutant, virus infection, fusion protein, respiratory, cold chain, distribution, Live virus, Delta variants, IgG titer, dose, Single-dose, Support, viral spike protein, acute respiratory syndrome, Endpoint, subunit, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, secondary endpoint, primary endpoints, Secondary endpoints, profile, subject, complex, neutralization potency, single-center, cohorts, alpha and delta variants, immunogenicity assessments, seroconversion rates, IgG titers, SAEs, SARS-CoV-2 viral infection, Cell, human IgG1 Fc, occurred, caused, healthy, conducted, receiving, SAE, skewed, the SARS-CoV-2, 【제목키워드】 Vaccine, phase, subunit,